Influence of drugs of abuse on neuronal morphology

描述：反复服用精神刺激药物，如 安非他明或可卡因，会产生持久的行为和神经生物学 被认为有助于相关长期后遗症的适应 毒品滥用，包括耐受性、敏感化、依赖性和成瘾。 一种形式的神经行为适应与成瘾有关。 通过行为敏感化现象，即过去的药物暴露 使个体对精神运动的激活和激励高度敏感 药物的激励作用。此应用程序的总体目标是更好地 了解反复暴露在空气中的长期神经生物学后果 精神刺激药物，这些药物在行为发育中所起的作用 敏感化，以及它们对上瘾的影响。更具体地说，我们有 最近发现，反复使用安非他明或可卡因治疗会产生 树突和树枝刺结构的持续变化 伏隔核和前额叶皮质两个脑区的神经元 明显地牵涉到调解毒品报酬。这些发现表明， 精神刺激性药物暴露改变大鼠突触连接模式 这些大脑区域可能也改变了这一神经的功能 电路。此应用程序的一个特定目标是进一步表征 精神刺激性药物在脑奖励中改变神经回路的能力 区域(使用高尔基技术)，并确定这些结构是否 适应与精神运动敏感化的发展有关。合而为一 我们将使用各种已知的程序来增加或 降低行为敏感化的强度或持久性以积累 关于结构适应程度的证据汇聚在一起 与行为现象共同变化。在其他实验中，我们将获得 关于精神刺激剂药物诱导的确切位置的更详细信息 中等刺神经元和锥体细胞上棘突密度的变化(即 仅限于树枝状树的一部分的结构变化)，以及 其他细胞群也受到影响。此外，我们将确定 药物自我给药经验是否对树突状细胞有影响 结构类似于实验者给药的结构，并且 接触自控可卡因的程度与 摄入量和形态适应的升级。终于在过去的一年里 在授权期内，我们会扩大调查范围，研究 药物诱导的可塑性对其他形式的经验依赖的影响 可塑性。具体地说，我们将测试接触精神刺激剂是否 药物在生命中的某个时刻限制了受影响的大脑区域的能力 在以后的生活中经历结构性适应，作为变化的结果 环境条件或与脑损伤恢复有关的。

DESCRIPTION: The repeated administration of psychostimulant drugs, such as amphetamine or cocaine, produces persistent behavioral and neurobiological adaptations that are thought to contribute to the long-term sequelae associated with drug abuse, including tolerance, sensitization, dependence and addiction. One form of neurobehavioral adaptation implicated in addiction is represented by the phenomenon of behavioral sensitization, whereby past drug exposure renders individuals hypersensitive to the psychomotor activating and incentive motivational effects of drugs. The overall aim of this application is to better understand the long-term neurobiological consequences of repeated exposure to psychostimulant drugs, the role these play in the development of behavioral sensitization, and their implications for addiction. More specifically, we have recently found that repeated treatment with amphetamine or cocaine produces persistent changes in the structure of dendrites and dendritic spines on neurons in the nucleus accumbens and prefrontal cortex, two brain regions prominently implicated in mediating drug reward. These findings suggest that exposure to psychostimulant drugs alters patterns of synaptic connectivity in these brain regions, presumably also altering the function of this neural circuitry. A specific aim of this application is to further characterize the ability of psychostimulant drugs to alter neural circuitry in brain reward regions (using the Golgi technique) and to determine whether these structural adaptations are related to the development of psychomotor sensitization. In one series of experiments we will use a variety of procedures known to increase or decrease the strength or persistence of behavioral sensitization to accumulate converging evidence regarding the extent to which structural adaptations co-vary with the behavioral phenomenon. In other experiments we will acquire more detailed information about the exact locus of psychostimulant drug-induced changes in spine density on medium spiny neurons and pyramidal cells (i.e., are structural changes confined to one portion of the dendritic tree), and whether other cell populations are also affected. In addition, we will determine whether drug self-administration experience produces effects on dendritic structure similar to those seen with experimenter-administered drug, and the relationship between the degree of exposure to self-administered cocaine, escalation of intake and morphological adaptations. Finally, in the last year of the award period we will expand the scope of our investigations to study the implications of drug-induced plasticity for other forms of experience-dependent plasticity. Specifically, we will test whether exposure to psychostimulant drugs at one point in life limits the ability of the affected brain regions to undergo structural adaptations later in life, as a consequence of changes in environmental condition or in association with recovery from brain damage.